N([O:3][C:4]([CH3:7])(C)C)=O.[NH2:8][C:9]1[S:10][C:11]2[C:19](=[O:20])[CH2:18][CH2:17][CH2:16][C:12]=2[C:13]=1[C:14]#[N:15].[C:21](#N)[CH3:22]>[Cu](Br)Br>[N:8]1([C:9]2[S:10][C:11]3[C:19](=[O:20])[CH2:18][CH2:17][CH2:16][C:12]=3[C:13]=2[C:14]#[N:15])[CH2:7][CH2:4][O:3][CH2:22][CH2:21]1Tert-butyl nitrite (4.6 mL, 4.3 mmol) was added to a cooled mixture of copper(II) bromide (10.5 g, 46.9 mmol) in acetonitrile (50 mL). 2-Amino-7-oxo-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile (6.0 g, 31.3 mmol) was then added over a period of 1 h and the reaction mixture was then allowed to warm to room temperature. The solvent was removed in vacuo and the residue was partitioned between DCM and 1M aqueous HCl. The organic phase was dried (magnesium sulfate) and concentrated in vacuo. The residue was purified by column chromatography (SiO2, 0-100% EtOAc/heptane) and the isolated product was combined with morpholine (4.5 mL) in DMSO (80 mL). The reaction mixture was heated at 100° C. for 1.5 h, then water (300 mL) was immediately added with rapid stirring and the mixture was allowed to cool to room temperature overnight. The precipitate was filtered off, washed with water and dried in vacuo to give the title compound (5.65 g, 69%) as a pale brown solid. δH (DMSO-d6) 3.80-3.72 (4H, m), 3.67-3.59 (4H, m), 2.73 (2H, t, J 6.0 Hz), 2.49-2.42 (2H, m), 2.13-2.03 (2H, m). LCMS (ES+) 263.2 (M+H)+.
Loading…
